Carolin K. Scriba
A5007135172- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Genomics and Rare Diseases
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Ion channel regulation and function
- Ophthalmology and Eye Disorders
- RNA and protein synthesis mechanisms
- Connective tissue disorders research
- Neurological diseases and metabolism
- Hereditary Neurological Disorders
- DNA Repair Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Fibroblast Growth Factor Research
- Pluripotent Stem Cells Research
- Parkinson's Disease and Spinal Disorders
- Neurological disorders and treatments
- Genetic Syndromes and Imprinting
- Mitochondrial Function and Pathology
- Cardiac electrophysiology and arrhythmias
Queen Elizabeth II Medical Centre
2020-2024
Harry Perkins Institute of Medical Research
2020-2024
The University of Western Australia
2020-2024
Pathwest Laboratory Medicine
2021-2022
Government of Western Australia Department of Health
2022
The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis.We sequenced the genomes of six persons with autosomal dominant LOCA who were members three French Canadian families and identified a candidate pathogenic repeat expansion. We then tested for association between expansion disease in two independent case-control series - one (66 patients 209 controls) other German (228 199 controls). also genotyped 20 Australian 31 Indian index patients. assayed gene protein...
More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing Oxford Nanopore’s ReadUntil function for parallel genotyping all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly DNA methylation profiling STR sites, from list predetermined candidates. This correctly diagnoses individuals...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause CANVAS. We screened an Asian-Pacific cohort for CANVAS novel repeat motif, (ACAGG)exp, three affected individuals. This motif associated with additional clinical features including fasciculations elevated serum creatine kinase. These have not previously been described individuals...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome is a progressive, generally late-onset, neurological disorder associated with biallelic pentanucleotide expansions in Intron 2 of the RFC1 gene. The locus exhibits substantial genetic variability, multiple pathogenic benign repeat alleles previously identified. To determine contribution to disease within an Australasian cohort further investigate heterogeneity exhibited at locus, combination flanking repeat-primed PCR was used...
ABSTRACT Individuals affected by inherited neuromuscular diseases often present with a specific pattern of muscle weakness, which can guide clinicians in genetic investigations and variant interpretation. Nonetheless, more than 50% cases do not receive diagnosis. Oculopharyngodistal myopathy (OPDM) is an manifesting particular combination ptosis, dysphagia distal weakness. Pathologically it characterised rimmed vacuoles intranuclear inclusions on biopsy. In recent years GCC • CCG repeat...
Nemaline myopathy (NM) is a congenital typically characterized by skeletal muscle weakness and the presence of abnormal thread- or rod-like structures (nemaline bodies) in myofibres. Pathogenic variants alpha actin gene, ACTA1, cause approximately 25% all NM cases. We generated two induced pluripotent stem cell lines from lymphoblastoid cells 4-month-old female with severe harbouring dominant variant ACTA1 (c.553C > A). The isogenic displayed characteristic iPSC morphology, expressed...
ABSTRACT Short-tandem repeat (STR) expansions are an important class of pathogenic genetic variants. Over forty neurological and neuromuscular diseases caused by STR expansions, with 37 different genes implicated to date. Here we describe the use programmable targeted long-read sequencing Oxford Nanopore’s ReadUntil function for parallel genotyping all known neuropathogenic STRs in a single, simple assay. Our approach enables accurate, haplotype-resolved assembly DNA methylation profiling...
RYR1 variants are the most common genetic cause of congenital myopathies, and typically central core disease (CCD) and/or malignant hyperthermia (MH). Here, we generated iPSC lines from two patients with CCD MH caused by dominant within region protein (p.Val2168Met p.Arg2508Cys). Both displayed typical morphology, uniform expression pluripotency markers, trilineage differentiation potential, had normal karyotypes. These first both MH. As these CCD/MH variants, should be useful to study...
RYR1 variants are a common cause of congenital myopathies, including multi-minicore disease (MmD) and central core (CCD). Here, we generated iPSC lines from two CCD patients with dominant missense that affect the transmembrane (pore) SPRY3 protein domains (p.His4813Tyr p.Asn1346Lys, respectively). Both had typical morphology, expressed canonical pluripotency markers, exhibited trilineage differentiation potential, normal karyotypes. Together existing lines, these represent important tools to...
Variants in MYH7 cause cardiomyopathies as well myosin storage myopathy and Laing early-onset distal (MPD1). MPD1 is characterized by muscle weakness atrophy usually beginning the lower legs. Here, we generated iPSC lines from lymphoblastoid cells of three unrelated individuals heterozygous for most common MPD1-causing variant; p.Lys1617del. showed typical morphology, expressed pluripotency markers, demonstrated trilineage differentiation potential, had a normal karyotype. These represent...
Central core disease (CCD) is a congenital disorder that results in hypotonia, delayed motor development, and areas of reduced oxidative activity the muscle fibre. Two induced pluripotent stem cell (iPSC) lines were generated from lymphoblastoid cells 33-year-old male with CCD, caused by previously unreported dominant c.14145_14156delCTACTGGGACA (p.Asn4715_Asp4718del) deletion RYR1 gene. Both demonstrated typical morphology, pluripotency, trilineage differentiation, had normal karyotype. As...
Nemaline myopathy (NM) is a congenital typically characterized by skeletal muscle weakness and the presence of nemaline bodies in myofibres. Approximately 25% NM cases are caused variants ACTA1. We generated two induced pluripotent stem cell lines from lymphoblastoid cells 10-year-old female with typical harbouring dominant pathogenic variant ACTA1 (c.541C>A). The isogenic displayed iPSC morphology, expressed pluripotency markers, could differentiate into each three germ layers. Although...
Nemaline myopathy (NM) is a congenital skeletal muscle disorder that typically results in weakness and the presence of rod-like structures (nemaline bodies) sarcoplasma and/or nuclei myofibres. Two induced pluripotent stem cell (iPSC) lines were generated from lymphoblastoid cells 1-month-old male with severe NM caused by homozygous recessive mutation ACTA1 gene (c.121C > T, p.Arg39Ter). The iPSC demonstrated typical morphology, expressed pluripotency markers, exhibited trilineage...
Variants in the ACTA1 gene are a common cause of nemaline myopathy (NM); muscle disease that typically presents at birth or early childhood with hypotonia and weakness. Here, we generated an induced pluripotent stem cell line (iPSC) from lymphoblastoid cells 3-month-old female patient intermediate NM caused by dominant variant (c.515C > A (p.Ala172Glu)). iPSCs showed typical morphology, expressed pluripotency markers, demonstrated trilineage differentiation potential, had normal karyotype....